Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets Versus Desvenlafaxine Succinate Sustained-release Tablets Targeting Anhedonia in Patients With Major Depression Disorder

Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets Versus Desvenlafaxine Succinate Sustained-release Tablets Targeting Anhedonia in Patients With Major Depression Disorder: a Multicentre, Open-label, Parallel-group, Randomised Controlled Trial

The purpose of this study is to evaluate efficacy and safety of toludesvenlafaxine hydrochloride sustained-release tablets in the treatment of anhedonia in patients with major depression disorder compared to desvenlafaxine succinate sustained-release tablets, to provide evidence-based basis for clinical rational drug use.

Study Overview

• Status: Recruiting
• Conditions: Anhedonia
• Intervention / Treatment: Drug: Toludesvenlafaxine hydrochloride sustained-release tablets; Drug: Desvenlafaxine succinate sustained-release tablets

Detailed Description

The study included 80 patients with major depression disorder (aged 18 to 65 years) who meet the diagnostic criteria for depression in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Eligible patients were randomly assigned (1:1) to 8-week treatment with toludesvenlafaxine hydrochloride sustained-release tablets (n=40) or desvenlafaxine succinate sustained-release tablets(n=40), followed up at period of enrollment as baseline and at the end of 2th, 4th and 8th weeks. Adverse events were recorded.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210024
      • Recruiting
      • Nanjing Brian Hospital
      • Contact: Hao Tang, MD; Phone Number: +8618913821366; Email: tanghao997@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects meet the diagnostic criteria for major depression disorder in the Diagnostic and Statistical Manual of Manual Disorders, fifth Edition (DSM-5);
• Male or female aged ≥18 and ≤65 years;
• Subjects who have a Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥24 points;
• Subjects who have a total score of Snaith-Hamilton Pleasure Scale (SHARPS) ≥3 points;
• Subjects voluntarily participate in the study and sign the informed consent form.

Exclusion Criteria:

• Allergic or known to be allergic to toludesvenlafaxine hydrochloride sustained-release tablets and desvenlafaxine succinate sustained-release tablets;
• Subjects have a severe self-injury/clear suicide attempt or behavior; Scores on MADRS items factor 10 ≥4 points;
• Subjects who meet the diagnostic criteria for any other psychotic disorders (except for major depression disorder) in DSM-5, or those who have substance disorders or drug abuse within the past six months;
• Individuals with severe and unstable physical diseases such as cardiovascular disease, liver disease, kidney disease, blood disorders, and endocrine disorders;
• Hypertensive patients with poor blood pressure control (systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg at screening);
• Total bilirubin (TBIL) values 1.5 times / alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2 times / creatinine (Cr) 1.2 times higher than the upper limit of normal, or Thyroid-stimulating hormone (TSH) outside the normal range at screening;
• Electrocardiogram (ECG) abnormalities that are clinically significant at period of screening and that the investigator considers as inappropriate conditions for inclusion, such as QTc interval >450 ms in men and QTc interval >460 ms in female;
• Pregnant or lactating women, recent planned pregnancy and unable to ensure effective contraception during the period;
• Other conditions that the investigator considers the participant is not suitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Toludesvenlafaxine hydrochloride sustained-release tablets treatment group	Drug: Toludesvenlafaxine hydrochloride sustained-release tablets; 80 mg or 120 mg or 160 mg orally once daily dosing for 8 weeks
Active Comparator: Desvenlafaxine succinate sustained-release tablets treatment group	Drug: Desvenlafaxine succinate sustained-release tablets; 50 mg orally once daily dosing for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Snaith-Hamilton Pleasure Scale (SHAPS) Total Score	The SHAPS is a well-validated 14-item self-report questionnaire commonly used to assess anhedonia. Each item on the SHAPS is worded so that higher scores indicate greater pleasure capacity. A total score can be derived by summing the responses to each item. Each item is rated as either 0 or 1, for a total score between 0 and 14	Baseline and the end of week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Snaith-Hamilton Pleasure Scale (SHAPS) Total Score	The SHAPS is a well-validated 14-item self-report questionnaire commonly used to assess anhedonia. Each item on the SHAPS is worded so that higher scores indicate greater pleasure capacity. A total score can be derived by summing the responses to each item. Each item is rated as either 0 or 1, for a total score between 0 and 14.	Baseline, the end of Week 2 and 4
Snaith-Hamilton Pleasure Scale (SHAPS) Reductive Rate	SHAPS Reductive Rate(%) = (pre-treatment score - post-treatment score)/pre-treatment score ×100%.	The end of Week 2, 4 and 8
Dimensional Anhedonia Rating Scale (DARS) Score	DARS is a 17-item self-report questionnaire that is designed to assess anhedonia in major depressive disorder (MDD), and particularly to increase scale generalizability while maintaining specificity. Respondents provide their own examples of rewarding experiences across the domains of hobbies, social activities, food/drink, and sensory experience. Participants answer a set of standardized questions about desire, motivation, effort, and consummatory pleasure with a recall period of "right now" for the examples provided. The instrument is scored as a total sum of all items (range 0-68) with higher scores reflecting increased motivation, effort and pleasure (that is, less anhedonia).	Baseline, the end of Week 2, 4 and 8
Montgomery-Asberg Depression Rating Scale (MADRS) Score	The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.	Baseline, the end of Week 2, 4 and 8
17-item Hamilton Depression Rating Scale (HAM-D17) Score	HAM-D17 has been the gold standard for the assessment of depression. The score needs to be based on clinical interviews, and the time frame of the assessment is usually the situation in the previous week. Most items use a 5-point scale of 0 to 4. The standard of each level is: 0 indicates none, 1 indicates mild, 2 indicates moderate, 3 indicates severe, and 4 indicates extremely severe. A few items adopt the 3-level scoring method with 0~2 points, and the grading standard is: 0 indicates none, 1 indicates mild to moderate and 2 indicates severe.	Baseline, the end of Week 2, 4 and 8
Sheehan Disability Scale (SDS) Score	SDS is composed of three self-rating dimensions, which assess functional status in work, social life/leisure activities, and family life/family responsibilities. Each dimension is scored on a scale of 0 to 10, with 1 to 3 indicating mild impairment, 4 to 6 indicating moderate impairment, 7 to 9 indicating significant impairment, and 10 indicating extreme severity. The three dimensions can also be added together to reflect the overall functional deficiency. The score ranges from 0 to 30, with 0 indicating no damage and 30 indicating significant damage.	Baseline, the end of Week 2, 4 and 8
Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Score	Q-LES-Q-SF consists of 16 self-rated items. Each item is divided into five grades: 1 indicates very dissatisfied, 2 indicates dissatisfied, 3 indicates average, 4 indicates satisfied, and 5 indicates very satisfied. The higher the score, the better the happiness and quality of life satisfaction of the subjects. The first 14 items are used to generate an overall score, while the remaining 2 items are individual items that measure satisfaction and overall quality of life related to the study drug.	Baseline, the end of Week 2, 4 and 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rating Scale for Side Effects (SERS) Score	All items in SERS adopt 4-level scoring method ranging from 0 to 3 points, and the standard of each item is as follows :0 indicates none, 1 indicates mild, 2 indicates moderate and 3 indicates severe. Two evaluation scales are required for each symptom. The first is the spontaneous reporting of patients when answering questions. The second is what the evaluator observed. The evaluator needs to systematically ask about each symptom.	The end of Week 2, 4 and 8
Arizona Sexual Experience Scale (ASEX) Score	ASEX is designed to assess aspects of psychotropic drug-induced sexual dysfunction: drive, arousal, penile erection/vaginal lubrication, ability to reach orgasm, and satisfaction from orgasm. The ASEX can be self- or clinician-administered. The 5 questions are rated using 6-point Likert-type scales with varying endpoints. Possible total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction.	Baseline, the end of Week 2, 4 and 8
Count of red blood cell in blood	To analysis whether count of red blood cell in blood show any significant trend with time changes.	Baseline, the end of Week 8
Count of white blood cell in blood	To analysis whether count of white blood cell in blood show any significant trend with time changes.	Baseline, the end of Week 8
Count of platelet in blood	To analysis whether count of platelet in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of hemoglobin in blood	To analysis whether concentration of hemoglobin in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of alanine aminotransferase in blood	To analysis whether concentration of alanine aminotransferase in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of aspartate aminotransferase in blood	To analysis whether concentration of aspartate aminotransferase in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of gamma-glutamyltransferase in blood	To analysis whether concentration of gamma-glutamyltransferase in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of blood glucose in blood	To analysis whether concentration of blood glucose in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of serum creatinine in blood	To analysis whether concentration of serum creatinine in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of urea in blood	To analysis whether concentration of urea in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of total cholesterol in blood	To analysis whether concentration of total cholesterol in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of high density lipoprotein in blood	To analysis whether concentration of high density lipoprotein in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of low density lipoprotein in blood	To analysis whether concentration of low density lipoprotein in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of triglyceride in blood	To analysis whether concentration of triglyceride in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of thyroid-stimulating hormone in blood	To analysis whether concentration of thyroid-stimulating hormone in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of protein in urine	To analysis whether concentration of protein in urine show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of sugar in urine	To analysis whether concentration of sugar in urine show any significant trend with time changes	Baseline, the end of Week 8
Count of white blood cell in urine	To analysis whether count of white blood cell in urine show any significant trend with time changes.	Baseline, the end of Week 8
Count of red blood cell in urine	To analysis whether count of red blood cell in urine show any significant trend with time changes.	Baseline, the end of Week 8
ECG QT Interval	To analysis whether ECG QT Interval of participants show any significant trend with time changes.	Baseline, the end of Week 8
Changes in weight	To analysis whether weight of participants show any significant trend with time changes.	Baseline, the end of Week 2, 4 and 8
Changes in pulse	To analysis whether pulse of participants show any significant trend with time changes.	Baseline, the end of Week 2, 4 and 8
Changes in both systolic and diastolic blood pressure	To analysis whether blood pressure including systolic blood pressure and diastolic blood pressure of participants show any significant trend with time changes.	Baseline, the end of Week 2, 4 and 8
Changes in respiration rate	To analysis whether respiration rate of participants show any significant trend with time changes.	Baseline, the end of Week 2, 4 and 8
Changes in armpit temperature	To analysis whether armpit temperature of participants show any significant trend with time changes.	Baseline, the end of Week 2, 4 and 8

Collaborators and Investigators

• Sponsor: Jiangsu Province Nanjing Brain Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: February 14, 2024
• First Posted (Actual): February 21, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Anhedonia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Desvenlafaxine Succinate
• Other Study ID Numbers: 2023-KY142-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No